Early life stress and inflammatory mechanisms of fatigue in the Coronary Artery Risk Development in Young Adults (CARDIA) study

Abstract

Fatigue is highly prevalent and causes serious disruption in quality of life. Although cross-sectional studies suggest childhood adversity is associated with adulthood fatigue, longitudinal evidence of this relationship and its specific biological mechanisms have not been established. This longitudinal study examined the association between early life stress and adulthood fatigue and tested whether this association was mediated by low-grade systemic inflammation as indexed by circulating C-reactive protein (CRP) and interleukin-6 (IL-6). In the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based longitudinal study conducted in 4 US cities, early life stress was retrospectively assessed in 2716 African-American and white adults using the Risky Families Questionnaire at Year 15 examination (2000-2001, ages 33-45 years). Fatigue as indexed by a loss of subjective vitality using the Vitality Subscale of the 12-item Short Form Health Survey was assessed at both Years 15 and 20. While CRP was measured at both Years 15 and 20, IL-6 was measured only at Year 20. Early life stress assessed at Year 15 was associated with adulthood fatigue at Year 20 after adjustment for sociodemographic characteristics, body-mass index, medication use, medical comorbidity, smoking, alcohol consumption, physical activity, current stress, pain, sleep disturbance as well as Year 15 fatigue (adjusted beta 0.047, P=0.007). However, neither CRP nor IL-6 was a significant mediator of this association. In summary, early life stress assessed in adulthood was associated with fatigue 5 years later, but this association was not mediated by low-grade systemic inflammation.

Figure 1. Independent baseline predictors of fatigue at follow-up 5 years later

Beta = standardized regression coefficient expressing the change in standardized outcome score per one standard deviation in early life stress measured as Early Family Environment; BMI = body-mass index * The figure shows significant baseline predictors of fatigue assessed 5 years later according to the multivariable model including the following variables: early life stress, age, gender, ethnicity, education, body-mass index, medication use, medical comorbidity, smoking, alcohol consumption, physical activity, current stress, pain, sleep disturbance, depression (CES-D score without fatigue and sleep items), and fatigue (all assessed at baseline, i.e., CARDIA Year 15). Hence, the beta was adjusted for all the above variables in testing the independent effect for each individual predictor. Baseline fatigue was obviously the strongest predictor of fatigue at follow-up (adjusted beta 0.373, P<0.001) but not shown in this figure.